On 1 January 2005, rubella infection during pregnancy and congenital rubella syndrome/infection (CRS/CRI) were made statutorily notifiable in Italy, as recommended by the national plan for the elimination of measles and congenital rubella [1]. This plan set a goal in 2003, to eliminate measles and reduce the incidence of congenital rubella cases to under 1 /100 000 live births by the year 2007. In Italy, rubella has been a statutorily notifiable disease since 1970, but reporting of congenital rubella (CR) was mandatory only between 1987 and 1991 and no specific surveillance of rubella in pregnancy has ever previously been conducted.

All suspected cases of rubella during pregnancy and congenital rubella must now be reported by physicians to the local health authorities. A suspected case of rubella during pregnancy can be in any woman in whom a physician suspects rubella, even if the signs and symptoms do not meet the clinical case definition (that is, acute onset of generalised maculopapular rash and arthralgia/arthritis, lymphadenopathy or conjunctivitis) [2]. This includes women with any nonvesicular rash illness in pregnancy, as well as asymptomatic women with positive rubella-specific IgM detected through prenatal screening. Based on clinical, laboratory and epidemiological findings, suspected rubella cases during pregnancy can be further classified as follows [2,3]:

a possible case is one that meets the clinical case definition

a probable case is one that is clinically compatible with rubella and that is epidemiologically linked to a confirmed case

a confirmed case is a clinically compatible case that is laboratory confirmed

an asymptomatic infection is a laboratory confirmed infection in a woman who is asymptomatic

A case that is initially reported as suspected, but after complete laboratory investigation lacks evidence of infection, is classified as not rubella.

Rubella vaccination has been recommended in Italy since 1972, and was initially targeted at pre-adolescent girls. Following the introduction of combined measles, mumps and rubella (MMR) vaccines in the early 1990s, a universal vaccination strategy targeting 15 month old children was adopted. Since 1999, the national immunisation schedule recommends MMR vaccine at 12–15 months of age, and a second dose at 5-6 or 11-12 years of age. National coverage by 24 months of age was estimated to be 56% in 1998, 78% in 2003, and 85% in 2004.

The last rubella epidemic in Italy occurred in 2002, with 6224 cases reported to the statutory notification system. A marked decrease in incidence has been observed since 2002, with a historical minimum of 139 cases reported in 2005 (provisional data, Ministry of Health), 12 of which occurred in women aged between 15-24 years, and four in women aged 25 to 64 years (Figure).

Between January and December 2005, nine cases of suspected rubella infection during pregnancy were reported. Follow up has so far been completed for seven of these cases, and they are described in this report. The other two cases are still being evaluated.

The seven cases were all reported by a university teaching hospital in Rome, where the women were referred after serologic rubella-specific IgM had been detected during pregnancy. To confirm IgM serology and differentiate recent rubella infections from reinfections, false-positive IgM results, or persistent IgM levels [4,5], further laboratory investigations were performed, including IgM and IgG kinetics, IgG avidity, and, in selected cases, amniocentesis for prenatal diagnosis. All infants born to mothers with confirmed infection were considered as suspected congenital rubella cases, and classified as follows [1]:

A suspected case was any infant born to a mother with confirmed rubella infection during pregnancy or with compatible clinical findings who did not meet the criteria for a probable case

A probable case was an infant in whom infection was not laboratory confirmed, but who had any two group a signs or symptoms(cataracts or congenital glaucoma, congenital heart disease, hearing impairment, or pigmentary retinopathy) or one group b sign or symptom(purpura, hepatosplenomegaly, jaundice, microcephaly, developmental delay, meningoencephalitis, or radiolucent bone disease), and where evidence for any other cause was lacking.

A confirmed case was an infant with a clinically consistent case that was laboratory confirmed.

An infant who demonstrated laboratory evidence of infection, but without any clinical symptoms or signs was classified as infection only.

Results
None of the seven women, who were aged between 23-37 years, had been vaccinated against rubella. Only one had undergone pre-conception rubella screening and had been found to be susceptible. Four of the seven women were Italian, two were from eastern Europe and one was from South America. For four women, this was their first pregnancy.

Rubella infection was confirmed in only two of the seven cases. Both confirmed cases occurred in women who had immigrated to Italy (one had acquired her infection in Peru), and both had presented with rash and fever, at 4 and 9 weeks gestation respectively. Prenatal diagnosis (amniocentesis at 19 and 21 weeks’ gestation) was performed in both women but virological analysis of amniotic fluid (virus isolation and PCR) was positive only in one case. At birth, this infant was found to have partial hearing loss and positive serum rubella-specific IgM and was therefore classified as having confirmed congenital rubella infection. The infant with negative prenatal virology did not present signs of congenital rubella infection at birth but was subsequently lost to follow up.

The five other cases had been found to have positive rubella-specific IgM titres between 7 and 20 weeks gestation but none of these women had presented with rash illness or other clinical signs or symptoms suggestive of rubella during the pregnancy. IgM positivity in these cases therefore either represented a false positive result or a rubella infection that had occurred before the pregnancy. One of the five women chose to terminate the pregnancy before 12 weeks gestation.

Conclusion
These cases reveal that rubella during pregnancy and congenital rubella infection do occur in Italy. Only one case of congenital rubella was identified, indicating an incidence of CR well below the elimination threshold of less than 1 case per 100 000 live births, which in Italy would be equivalent to 5 CR cases. These data, however, probably represent marked underreporting. All cases were notified by the same hospital centre in Rome, and so we assume that many more unreported cases occur across Italy. This indicates a need for improved training of physicians regarding the necessity of reporting cases of suspected rubella in pregnancy and of congenital rubella.

Only two of the seven reported cases were confirmed, while in five cases rubella infection had been suspected because of a positive specific IgM result. This confirms that the diagnosis of acute rubella infection in pregnant women should never be never solely on serologic detection of rubella-specific IgM antibodies [4]. In fact, positive IgM results should be interpreted with extreme caution, especially in pregnancy, when women may be faced with the decision to terminate the pregnancy.

In addition to ensuring high MMR vaccination coverage with the universal routine childhood immunisation programme, rubella susceptibility testing of women of childbearing age (preconception screening) and postpartum vaccination of susceptible women are essential in order to prevent the occurrence of rubella infections during pregnancy and therefore congenital rubella cases. Physicians must use every opportunity, such as consultations for contraception or travel advice, to review the vaccination history of women of childbearing age. Physicians should also be aware that many women who immigrate to Italy come from countries without rubella vaccination programmes, and, efforts should therefore be made to immunise newly-arrived adolescents and women of childbearing age against rubella [6].

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